Proteome Profiling Identifies Markers for Inflammation-Related Tumor-Fibroblast Interaction in Colorectal Cancer

ABSTRACT: Inflammation has been identified as an important factor in cancer development and progression, including colorectal cancer [CRC]. To determine the role of inflammation and the specific contribution of activated fibroblasts in cancer development and progression we analyzed six human CRC tissue specimens and paired normal adjacent mucosa samples by LS/MS-MS. Amongst other, indeed several inflammation associated proteins were found differentially expressed compared to normal colonic mucosa. Two candidate molecules, SPARC and THBS2 were recently identified as proteins of a fibroblast inflammation signature. Analysis of public available RNA expression datasets revealed, that the mRNA of both SPARC and THBS2 are upregulated in CRC, typically in association with the CRC consensus molecular subtype 4 [CMS4]. Immunohistochemistry staining also demonstrated upregulation of SPARC and THBS2 in the tumor stroma compared to normal adjacent mucosa and indicated co-localization with the mesenchymal marker [alpha]SMA. In vitro 3D co-culture experiments with human colon derived fibroblasts and CRC cell lines resulted in enhanced SPARC and THBS2 protein levels when both cell types were cultivated in direct physical contact, compared to fibroblasts or cancer cells alone. This study demonstrates the feasibility of detecting tumor-specific signatures by LC-MS/MS and compatibility with RNA expression datasets. We identified an inflammation signature in CRC tissue and the data emphasized the contribution of activated fibroblasts in these events.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

DISEASE(S): Colorectal Cancer

SUBMITTER: Christopher Gerner  

LAB HEAD: Christopher Gerner

PROVIDER: PXD006776 | Pride | 2018-10-17

REPOSITORIES: Pride